From 1979 through July 1983, 859 patients were enrolled in a Phase III RTOG Protocol (7916) evaluating the role of Misonidazole combined with radiation in the treatment of brain metastasis. Patients were randomized to one of four treatment arms (3.0 Gy x 10 fractions with or without 1 g/m2 of Misonidazole [total 10 g/m2] versus 5.0 Gy x 6 fractions with or without 2 g/m2 of Misonidazole) [total 12 g/m2]. Among the 779 analyzable cases, 63% had a lung primary and 12% had breast. Of the histologic types, 43% were adenocarcinoma and 24% were squamous cell. Seventy-eight percent had a Karnofsky of greater than 70. Of the 779 cases, 773 are dead (99%). Median survival is 3.9 months, with 60% alive at 3 months, 35% at 6 months, and 15% at 1 year. Survival was evaluated by treatment arm, Misonidazole status, and fractionation scheme; none showed any statistical significance. Favorable prognostic factors were assessed (age less than 60, Karnofsky of 70-100, controlled primary and brain metastasis only) in each treatment arm and no difference was found. Brain metastasis was cause of death in 1/3, and 19-33% of patients were retreated. Because up to 1/3 of the patients in this study died secondary to uncontrolled brain metastasis, improvement in local control remains an important goal. Until proven otherwise, the treatment of choice for the majority of patients still remains a conventional palliative course of 3.0 Gy x 10 fractions.