untreated nervous central metastases cns active symptomatic brain known progressing cns metastases nervous central symptomatic untreated neurologically patients known primary cns metastases symptomatic untreated patients active known uncontrolled excluded brain excluded subjects metastases brain clinical trial cancers treated cns primary brain symptomatic metastases inclusive uncontrolled requiring corticosteroids limited concurrent radiation metastases brain known participants excluded patients corticosteroids treated imaging clinical brain metastases excluded trial clinical known patients participants untreated symptomatic