Figure 1. CONSORT Diagram.

^aTwo enrolled patients did not undergo baseline brain magnetic resonance imaging (1 in the tucatinib-combination group and 1 in the placebo-combination group).

^bTucatinib, trastuzumab, and capecitabine.

^cPlacebo, trastuzumab, and capecitabine.

^dPatients with brain metastases that were previously treated and did not progress since most recent CNS-directed therapy.

^ePatients with brain metastases that were either untreated or previously treated and progressed since most recent CNS-directed therapy.

^fOriginal randomized treatment, not including crossover.