Drupal 8 no longer detects changes to either the set of regions of a theme or simply name changes after a cache clear; this information is stored in State and unfortunately only updated when either a theme is disabled or enabled, or a module is installed or uninstalled.
This is a terrible Themer Experience. It's also a regression compared to Drupal 7, where I was able to have the changes be detected by simply clearing all caches.
I propose a simple solution: refreshing this info whenever saving a theme's configuration. Adding the following snippet to ThemeSettingsForm::submitForm() fixes the problem:
// Also refresh the theme info, to ensure new or modified regions are detected.
\Drupal::service('theme_handler')->refreshInfo();