Context: In patients with brain metastases, it is unclear whether adding up- front whole- brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. Objective: To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. Design, Setting, and Patients: Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. Interventions: Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). Main Outcome Measures: The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. Results: The median survival time and the 1- year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7% - 50.3% ) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6% - 39.2% ) for SRS alone (P=.42). The 12- month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P < .001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P < .001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P=.64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. Conclusions: Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up- front WBRT is not used. Context: In patients with brain metastases, it is unclear whether adding up- front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. Objective: To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. Design, Setting, and Patients: Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. Interventions: Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). Main Outcome Measures: The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. Results: The median survival time and the 1- y ear actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7% - 50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6% - 39.2% P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for the SRS alone group (P <.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P <.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. Conclusions: Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Effects, salvage treatment is frequently requiredwhen up- front WBRT is not used.